Role of TSC/mTOR signaling pathway in autism and autism spectrum disorders

Vijaya Ramesh and her colleagues will investigate whether genes linked to tuberous sclerosis are also associated with autism spectrum disorders. The TOR pathway, which is named for a key protein that receives information on the cell surface, controls the growth of many cells and regulates the connections neurons make with each other. Without this pathway, neurons have trouble finding each other or signaling to each other, two potential deficits in autistic brains. Ramesh and her colleagues plan to examine the genes of several components of the TOR pathway, looking for mutations that are associated with autism. By narrowing their focus, the researchers will be able to analyze more samples (from about 300 autistic individuals), and with a greater attention to detail in the candidate genes. Once one mutation is linked to autism, the researchers can try to find the mutation among more people with autism to make the correlation stronger. The team will also perform assays in cultured neurons to see how the mutations affect TOR pathway activity. The mutations associated with tuberous sclerosis often remove the negative regulators of the TOR pathway, allowing it to signal uncontrolled; the relationship between the two disorders suggests that autism-linked mutations would have a comparable effect on TOR pathway signaling. If so, the findings would hint at a new therapy for autism, perhaps based on the available drugs that can efficiently inhibit the TOR pathway.